Abstract

Background: The monitoring of regional cerebral O2 saturation (rSO2) with near-infrared spectroscopy (NIRS) is a noninvasive technique to measure tissue oxygenation in the brain. It may be an effective monitoring technique in the early diagnosis of pre-, intra- and post-operative insufficient oxygen supply to the brain in surgery for congenital heart diseases. In pediatric patients, a variety of clinical and laboratory parameters, including serum lactate and regional cerebral oxygen saturation, may be helpful in monitoring global tissue and cerebral oxygen delivery and consumption.

Aim: Our study was designed to investigate whether there is a correlation between the NIRS scores and serum lactate levels during congenital heart surgery. Our secondary objective was to define the predictive value of this correlation on the duration of extubation and intensive care unit stay.

Method: A total of 82 successive neonatal and infant patients with complex cardiac pathologies were enrolled in the study. Blood lactate levels and NIRS values were measured during the phases of anesthesia induction, sternotomy, cannulation, onset of CPB, the beginning of aortic cross-clamping and the end of the CPB.

Study Design: Prospective randomized Results: Patients with normal rSO2 /normal lactate during the operation represented the largest percentage of patients during anesthesia induction (n=50, 60.9%) and sternotomy (n=54, 65.8%). The only negative correlation between lactate and rSO2 was detected during anesthesia induction. The time to extubation and the stay in the intensive care unit were longer in patients with low rSO2 values during anesthesia induction and sternotomy. In the same periods, elevated lactate levels were associated with longer time to extubation and intensive care unit stay than the patients with normal lactate levels.

Conclusion: In our study, no correlation was demonstrated between NIRS scores and serum lactate levels in children during congenital heart surgery, except for anesthesia induction. The only negative correlation between the decrease in NIRS scores and the increase in serum lactate levels was observed during anesthesia induction. This result indicated that cerebral NIRS monitoring cannot be used as an indicator of global hypoperfusion in the same way as lactate.

Keywords

Lactate, Near infrared spectroscopy, Congenital heart diseases

Introduction

Due to advances in myocardial protection, surgical techniques,
cardiac anesthesia and postoperative care in recent decades,
many congenital heart diseases have been surgically treated
with acceptable mortality rates [1]. Although mortality rates
have decreased to 3 percent, morbidity is still relatively high in
infants undergoing complex cardiac surgical procedures [2,3].

Complex cardiac pathologies are the multiple ones occurring
together. Morbidity is thought to be related to inadequate tissue
oxygen delivery due to impaired cardiac output, which is a
relatively common problem after pediatric cardiac surgery [4].
Intraoperative deterioration in regional cerebral oxygen
saturation (rSO2) has also been identified as a potential
contributor to neurologic outcomes among children undergoing cardiac surgery [5]. Therefore, the early identification and
correction of impaired global tissue perfusion or cerebral blood
flow may be expected to decrease the morbidity and mortality
of these critical patients. In pediatric patients, a variety of
clinical and laboratory parameters, including serum lactate and
regional cerebral oxygen saturation, may be helpful in
monitoring global tissue and cerebral oxygen delivery and
consumption. The level of serum lactate is one of the best
indicators of cardiac output, oxygen supply and cellular
perfusion [6]. Elevated serum lactate levels during congenital
cardiac surgery are associated with poorer outcomes. They
mainly appear to be related to an imbalance between oxygen
delivery and needs during cardiopulmonary bypass (CPB) or
after cardiac surgery [1,7,8]. However, the utility of lactate
measurement may be limited because of the need for
intermittent blood sampling.

The monitoring of regional cerebral O2 saturation (rSO2) with
near-infrared spectroscopy (NIRS) is a noninvasive technique
to measure tissue oxygenation in the brain [9]. It may be an
effective monitoring technique in the early diagnosis of pre-,
intra- and post-operative insufficient oxygen supply to the
brain in surgery for congenital heart diseases [10]. In addition,
the use of NIRS has expanded to examine oxygenation in other
tissues and to estimate the adequacy of systemic circulation
[11]. If a correlation between NIRS measurements and lactate
levels can be demonstrated, then it will ensure more reliable
monitoring for cardiac output, earlier diagnosis of global tissue
perfusion and earlier intervention. This study was designed to
investigate whether there is a correlation between the NIRS
scores and serum lactate levels during congenital heart surgery.
Our secondary objective was to define the predictive value of
this correlation on the duration of extubation and intensive care
unit stay.

Patients and Methodology

Patients and study design

This was a prospective study of the infants with congenital
heart diseases who underwent corrective surgery between
September 2012 and May 2013 at a university hospital. The
study was approved by the institutional ethics committee of the
university. A total of 82 successive neonatal and infant patients
with complex cardiac pathologies were enrolled in the study.
Emergency cases, off-pump surgeries, hemodynamically
unstable patients during the preoperative period, and infants
weighing less than 2 kg were excluded from the study.

Monitoring of the patients

Noninvasive monitoring included electrocardiography, pulse
oximetry, and analysis of inspiratory and expiratory gas
concentrations. The body temperature of the patients was
continuously measured from the nasopharynx. The right
femoral artery and right internal jugular vein were catheterized
for the measurement of arterial pressure and central venous
pressure, respectively. Near infrared spectroscopy monitoring
was performed continuously using a NIRS sensor (INVOSTM-5100 C, Medtronic Inc., Minneapolis, MI, USA)
attached on the forehead of the patients. The first NIRS score
after induction of anesthesia was considered the baseline rSO2.

Anesthetic management

All patients over 6 months of age were pre-medicated using
oral midazolam (0.5 mg/kg) preoperatively. Anesthesia was
induced with inhalation of sevoflurane (6 %) in a 70% O2 +
30% air mixture. After accessing the intravenous line, fentanyl
(3 mcg/kg) and rocuronium (0.6 mg/kg) were administered
intravenously, and the patients were intubated. Anesthesia was
maintained with 2% sevoflurane in the oxygen-air mixture and
intermittant fentanyl and rocuronium boluses were
administered.

Intraoperative management of patients

All operations were performed by the same team of two
cardiac surgeons during the study period. Cardiac procedures
were performed in all patients using median sternotomy.
Following systemic heparinization (4 mg/kg), the aorta and
superior and inferior vena cava were cannulated and
cardiopulmonary bypass (CPB) was initiated. Pulsatile
perfusion was achieved using a pulsatile roller pump (Maquet
HL20, Hirrlingen, Germany). During CPB, hematocrit, mean
arterial pressure and arterial oxygen saturation were
maintained at 28-35%, 40 mmHg and 70-90%, respectively.
Myocardial protection was achieved with blood cardioplegia
applied at 20-minute intervals. Hypothermic circulatory arrest
was not performed in any patient. At the end of the surgical
correction, dopamine and milrinone were initiated routinely at
low-moderate doses to maintain a mean pressure at 40 mmHg,
and CPB was terminated. In cases of need, doses were
adjusted. In required patients, modified ultrafiltration was
applied. In cases of regional cerebral oxygenation
deterioration, the algorithm in the use of brain oximetry
proposed by Denault et al. was used to treat the decrease in
rSO2.

Measurements

Blood lactate levels, obtained from the peripheral arterial line,
were measured during the phases of anesthesia induction,
sternotomy, cannulation, onset of CPB, the beginning of aortic
cross-clamping and the end of the CPB. A lactate level over 3
mmol/L was considered to represent hyperlactatemia. Heart
rate, mean arterial pressure, temperature, pH, PaCO2, PaO2,
SaO2, and hematocrit level were recorded in the same time
periods. The duration of cardiopulmonary bypass, the amounts
of blood products used, duration of the surgery, the time to
extubation and intensive care unit (ICU) stays were also
recorded.

Statistical analysis

Power analysis was performed in G Power 3.1.9.2, and based
on previous studies 95% actual power, total sample size was
found to be 72 patients. Categorical values and continuous numerical data were analyzed using the chi-square and Mann-
Whitney U tests, respectively. Pearson’s correlation coefficient
was employed to compare lactate and NIRS levels. p<0.05 was
accepted as the level of significance. All values were presented
as mean ± standard deviation.

Results

The patients’ demographics and operative variables are
summarized in Table 1 and Table 2.

Most of the patients included in study had tetralogy of Fallot
(n=12), ventricular septal defect (n=12), followed by atrial
septal defect (n=10), atrioventricular septal defect (n=10) and
transposition of great arteries (n=8). Three patients died
following Benthall operation, Norwood Stage 1, and arterial
switch operation.

Patients with normal rSO2/normal lactate during the operation
represented the largest percentage of patients during anesthesia
induction (n=50, 60.9%) and sternotomy (n=54, 65.8%)
(Figure 1). During CPB, the percentage of patients with
abnormal rSO2 or lactate was higher than that of patients with
normal rSO2/ normal lactate in all measurement phases. The
only negative correlation between lactate and rSO2 was
detected during anesthesia induction.

Figure 1: Intraoperative serum lactate and rSO2 correlation (n)

Postoperative variables

The time to extubation and the stay in the intensive care unit
were longer in patients with low rSO2 values during anesthesia
induction and sternotomy (p=0.008, p=0.001, respectively)
than the patients with normal NIRS values during the same
time periods. In the same periods, elevated lactate levels were
associated with longer time to extubation and intensive care
unit stay than the patients with normal lactate levels (p=0.03).
The decrease in rSO2 at the onset of CPB and the increase in
serum lactate during cross clamping were associated with time
to extubation and intensive care unit stay (p=0.017, p=0.037,
respectively) (Figures 2-5). Upon the termination of CPB, a
significant increase in blood lactate levels of 34 patients was
recorded, which was not significantly correlated with
extubation time and intensive care unit stay (Figures 3 and 4).

Figure 2: Extubation time (days) of the patients with and without a
decrease in NIRS scores. p=0.008 at induction and sternotomy.
p=0.017 at CPB-on.

During anesthesia induction, a negative correlation was
detected in between the decrease in NIRS scores and the
increase in lactate levels (p=0.01). In all other measurements,
this negative correlation did not reach significant levels.

Discussion

In this study, we demonstrated that low NIRS and high lactate
levels were associated with an increased risk of prolonged time
to extubation and intensive care unit stay in children undergoing congenital heart surgery. However, we failed to
demonstrate a correlation between NIRS scores and serum
lactate levels during congenital heart surgery except for the
negative correlation during anesthesia induction. This result
indicated that cerebral NIRS monitoring cannot be used as an
indicator of global hypoperfusion in the same way as lactate
during congenital heart surgery.

Inadequate tissue oxygen delivery due to impaired cardiac
output is a relatively common problem during pediatric cardiac
surgery. Global or regional tissue hypoperfusion should be
diagnosed early and treated immediately to prevent organ
dysfunction and organ failure in these patients [12]. Routinely
monitored parameters, such as blood pressure, heart rate,
arterial oxygen saturation, and urine output, may not reflect the
adequacy of global perfusion in these patients. Therefore,
various clinical indicators and biochemical markers reflecting
tissue perfusion and systemic oxygen delivery have been
commonly investigated to gauge the adequacy of tissue oxygen
delivery during this critical time period [12]. Blood lactate has
been studied as a potential clinical marker of global
hypoperfusion after cardiac surgery, particularly in children
[4,13,14]. In these studies, elevated lactate levels were reported
to be associated with metabolic acidosis, tissue hypoperfusion
and hypoxia during cardiac surgery with cardiopulmonary
bypass (CPB).

Elevated lactate levels as a result of impaired cardiac output
have been associated with significant morbidity and mortality
after pediatric cardiac surgery. [14,15] Therefore, multiple
studies of pediatric data have examined the utility of blood
lactate levels as both positive and negative predictors of
outcome after surgery for CHD [1,8,16-18]. Basaran et al.
demonstrated the presence of a correlation between high lactate
levels detected in the early postoperative period and mortality
in 60 patients who would undergo surgery to treat their
congenital heart disease [1]. In addition, they stated that high
lactate levels correlated significantly with inotrope score,
intubation time, and duration of intensive care unit stay.
Similarly, Charpie et al. [8] demonstrated that high lactate
levels were a predictor of mortality within 72 h of surgery or
the need for extracorporeal membrane oxygenation support in
infants undergoing complex cardiac surgeries. Cheifetz et al.
[17] demonstrated that lactate levels of the infants aged <1 year
who had undergone cardiopulmonary bypass were very useful
as markers of mortality. Hatherill et al. [18] also demonstrated
that children with a complicated post-operative course had
higher median serum lactate levels than patients with an
uncomplicated course.

Similarly, in our study, increases in serum lactate levels during
surgery were found to be correlated with increases in the
duration of postoperative extubation and ICU stay. A positive
correlation between hyperlactatemia and postoperative
negative outcome forces clinicians to prevent, detect and treat
the increase of serum lactate levels during pediatric cardiac
surgery. Levels of lactate maintained at high levels following a
complex surgery should be assigned importance as markers of
mortality. If discerned in time, during this worsening disease progression, aggressive measures, which increase both cardiac
output and arterial oxygen content, should be taken
prematurely. Every effort should be made to increase cardiac
output by optimizing heart rate, increasing preload, correcting
ventricular contractility and decreasing afterload. Additionally,
arterial oxygen content should be enhanced by increasing
oxygen saturation of the inspiratory air and normalizing
hemoglobin values. Adjusted oxygen supply will improve
survival rates. Therefore, every method that can discern
disequilibrium between oxygen demand and supply at an early
stage is important.

Despite the fact that a correlation between lactate levels
coursing at high levels and morbidity in pediatric cardiac
surgery was demonstrated, the continuous measurement of
lactate levels was not possible due to its invasive nature.
Additionally, measurements at intervals may delay the
recognition of deranged tissue perfusion. Therefore,
considering the study performed by Chakravarti et al. [4], who
demonstrated the presence of a serious negative correlation
between high lactate levels and low NIRS values, we believed
that we could discern the state of hypoperfusion at an early
stage using continuous monitoring with NIRS measurements
rather than intermittent lactate evaluations. Monitoring
regional cerebral oxygen saturation (rSO2) with near-infrared
spectroscopy (NIRS) is a noninvasive, continuous, and real-time
measurement technique that monitors brain tissue oxygen
saturation through the measurement of oxyhemoglobin and de-oxyhemoglobin
concentrations. [9,10,19,20] NIRS provides
valuable information not only about cerebral oxygenation but
also about the oxygenation of systemic tissues [21]. Previous
studies have provided some evidence that low rSO2 values
reflect impaired global tissue perfusion and the development of
organ dysfunction [22]. There is increasing evidence that low
rSO2 values are associated with adverse neurological outcomes
and death in congenital heart surgery. In a retrospective review
of HLHS patients undergoing Norwood Stage I palliation,
Phelps et al. [23] determined the relationship between mean
rSO2 in the 48 hours postoperatively, with death, need for
ECMO, and prolonged ICU stay >30 days. In the study of Dent
et al. [24], a prolonged low rSO2 (>180 minutes with< rSO2 45%) was associated with a higher risk of new ischemic lesions
on postoperative MRI when compared to the pre-surgical study
in neonates undergoing the Norwood operation. Slater et al.
[25] demonstrated that prolonged desaturation time observed in
NIRS extends the period of hospital stay after cardiac surgery.
Chakravarti et al. [4] also stated that low cerebral NIRS
readings below 45% at any time point was correlated with
postoperative mortality. In the first 24 postoperative hours, a
mean arterial lactate level >9.3 mmol/L was correlated with
adverse clinical events, primarily ECMO and death. In our
study, the duration of extubation and ICU stay were found to
be longer in patients with lower NIRS scores than the patients
with normal NIRS scores. It should be emphasized that
hemoglobin and PaCO2 levels during cardiac surgery have an
impact on NIRS measurements. Hemodilution and reduced
PaCO2 will decrease NIRS scores by decreasing the cerebral
blood flow rate [26]. Despite our efforts to keep these values at similar levels, we believe that all of these subfactors effected
the outcome of our study.

The correlation of intraoperative regional oxygen saturation
(rSO2) estimated by near-infrared spectroscopy with serum
lactate levels in infants with congenital heart disease who had
previously undergone cardiac surgery has been investigated
[21]. In a prospective study, the averaged cerebral and renal
rSO2 was found to be a good predictor of lactate, with a value
less than or equal to 65%, predicting a lactate level of greater
than or equal to 3.0 mmol/L with a sensitivity of 95% and a
specificity of 83% in the patients investigated. Furthermore,
the authors claimed that rSO2 may be an early indicator of
impaired oxygen delivery to the tissues, and the monitoring of
rSO2 could aid in the prompt identification of patients at risk
for low cardiac output syndrome [4]. In contrast, Bhalala et al.
[27] reported that splanchnic and/or renal hypoxemia as
detected by near-infrared spectroscopy may not be an accurate
indicator of low cardiac output after surgery for congenital
heart defects. Similarly, Dodge-Khatami et al. [20] reported
that they found a weak correlation between either cerebral or
renal NIRS with lactate levels when the full 24 postoperative
hours were considered. However, when each time point was
considered separately, they found that cerebral rSO2 readings
had a strong inverse correlation with arterial lactate levels up to
6 hours and lesser so thereafter until study completion. During
states of low cardiac output, cerebral blood flow and thus
cerebral NIRS may be better preserved than in somatic tissue
sites. The physiological protection mechanism of cerebral
blood flow may explain the lack of the correlation between
NIRS scores and blood lactate levels during low cardiac output
situations. Ciccone et al. demonstrated in their study that
different degrees of maturity influence morpho-functional
cardiac alterations during the transitional period [28]. In our
study different ages and different pathologies of the children
might be another reason for the results. In our study, no
correlation was demonstrated between NIRS scores and serum
lactate levels in children during congenital heart surgery,
except for anesthesia induction. The only negative correlation
between the decrease in NIRS scores and the increase in serum
lactate levels was observed during anesthesia induction. This
result indicated that cerebral NIRS monitoring cannot be used
as an indicator of global hypoperfusion in the same way as
lactate.

Limitations

The most important limitation of our study was that despite
long-term follow-ups of our patients, we did not record long-term
outcomes of these patients using neurological tests.
Patient sample size could be larger. So in a similarly designed
study with a larger sample size, we aimed to evaluate and
present the outcomes of long-term neurological innovations.
We believe that in the future, using a combination of serial
lactate measurements and NIRS monitorization, modifications
that will change the direction of the treatment without a loss of
time would be made. Thus, it will be possible to correct lower cardiac output with an early intervention [12] in children
undergoing congenital heart surgery.

Acknowledgements

The English in this document has been checked by at least two
professional editors, both native speakers of English.